ERMARD

Chr 6AD

ER membrane associated RNA degradation

Also known as: C6orf70, PVNH6, dJ266L20.3

NCBI Gene: 55780 ENSG00000130023 UniProt: Q5T6L9 OMIM: 615532

This endoplasmic reticulum membrane protein with two transmembrane domains is required for proper neuronal migration during brain development. Mutations cause periventricular nodular heterotopia-6 (PVNH6), a malformation where neurons fail to migrate from the ventricular zone and form nodules along the lateral ventricles, inherited in an autosomal dominant pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene contains 2 transmembrane domains near the C-terminus and is localized in the endoplasmic reticulum. Knockout of this gene in developing rat brain showed that it may be involved in neuronal migration. Mutations in this gene are associated with periventricular nodular heterotopia-6 (PVNH6). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2013]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 1.021 OMIM phenotype

Clinical Summary— ERMARD

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Gene-Disease Validity (ClinGen)

periventricular nodular heterotopia · ADLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 197 VUS of 383 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.44

OE 0.75 (0.56–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.32Z-score

OE missense 1.05 (0.96–1.14)

384 obs / 366.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.75 (0.56–1.02)

0≤0.351.4

Missense OE?1.05 (0.96–1.14)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 29 / 38.6Missense obs/exp: 384 / 366.8Syn Z: -0.40

ClinVar Variant Classifications

383 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic2

VUS197

Likely Benign115

Benign52

Conflicting16

Pathogenic

Likely Pathogenic

197

VUS

115

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	2	0	0	0	2
VUS	24	162	8	3	197
Likely Benign	0	23	47	45	115
Benign	0	7	38	7	52
Conflicting	—				16
Total	26	193	93	55	383

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

80 pathogenic / likely-pathogenic (of 86) ClinVar copy-number / structural variants overlap ERMARD — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →